DEVELOPMENT AND SYNTHETIC APPLICATION FOR STEREOSELECTIVE MICHAEL/ALDOL TANDEM REACTION TRIGGERED BY THIOLATE ANION

对Michael/aldol串联反应进行了研究，发现了以下几个新的进展：1）发现该反应不仅适用于不饱和酯，而且适用于不饱和酰胺。使用该程序可以轻松制备酰胺-贝利斯-希尔曼加合物，而在经典的贝利斯-希尔曼反应条件下很难合成该加合物。2）使用镁离子作为硫醇盐的抗衡阳离子为反应开辟了一个新的方面，即对羟醛缩合反应表现出相反的非对映选择性。在这些条件下，抗醛醇的制备被认为是有限的。我们还尝试捕捉反应中间体来理解反应机理，发现α-硫代醇盐是反应的中间体; 3）通过本方法发展了一种制备多取代四氢呋喃的简便方法; 4）研究了自由基消除反应的区域化学。实现了串联加合物向α，β-不饱和酯或β，γ-不饱和酯的区域选择性转化。这一结果是在自由基消除反应中区域控制的第一个例子。5）我们完成了硫醇到不对称取代的富马酸酯的串联或Michael反应的第一个区域控制。

The titled reaction, the Michael/aldol tandem reaction, was investigated and found the following developments.1) We found this reaction can be applied to not only unsaturated esters but also unsaturated amides. Use of the procedure makes it easy to prepare amide-Baylis-Hillman adducts, which was difficult to synthesize under classical Baylis-Hillman reaction conditions. It should be mentioned that our reaction condition requires no special protection for the acidic amide NH proton for the progress of aldol reaction.2) Use of magnesium ion as a counter cation of thiolate opens the new aspect of the reaction that shows opposite diastereoselectivity for the aldol reaction. Under these conditions, anti-aldols, the preparation of which are recognized to be limited. We have also attempted to catch the reaction intermediate to understand the reaction mechanism, and found that a-thioalkoxide is the intermediate of the reaction.3) We have developed a new ready method to prepare multi-substituted tetrahydrofurans through the present method.4) Regiochemistry of radical elimination reaction was investigated. The regioselective transformation of the tandem adducts to α, β-unsaturated or β, γ-unsaturated ester was accomplished. This result is the first example of the regiocontrol in the radical elimination reaction.5) We have accomplished the first regiocontrol of the tandem or the Michael reaction of thiol to unsymmetrically substituted fumaric ester.